QSAR Study of Novel Benzothiophene Derivatives as Potent Anticancer Agent

Abstract

Benzo[b]thienyl hydroxamic acids, a novel class of histone deacetylase (HDAC) inhibitors, were identified via a targeted screen of small molecule hydroxamic acids. Quantitative structure activity relationship (QSAR) analysis was performed on a series of Benzo[b]thiophene-based histone deacetylase inhibitors for their anticancer activity by using VLife MDS software. QSAR models were generated based on various statistical methods like Multiple Regression, Principal Component Regression, Partial Least Squares Regression etc. QSAR study revealed that steric, electrostatic interactions, electro-topological parameters, estate numbers and alignment independent descriptors are primarily responsible for anticancer activity. QSAR model demonstrated that anticancer activity is correlated with some of the parameters viz. T_2_N_1, PolarSurfaceAreaIncluding P and S, T_2_S_7, T_C_C_4, T_C_N_4, SaaCHE-Index, T_N_S_4, and SaasCE-Index etc. The best model showed r2 value = 0.9412 and this model was obtained from Multiple Regression method with good predictive ability. The results obtained from QSAR studies could be used in designing better anticancer agents among the congeners in future. Keywords: HDAC, Histone deacetylase inhibitor, HDAC inhibitor, Anticancer drug, SAHA, Hydroxamic acids, Benzo[b]thiophene.